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WO2002038139A1 - Preparation pharmaceutique du type a absorption percutanee - Google Patents

Preparation pharmaceutique du type a absorption percutanee Download PDF

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Publication number
WO2002038139A1
WO2002038139A1 PCT/JP2001/009496 JP0109496W WO0238139A1 WO 2002038139 A1 WO2002038139 A1 WO 2002038139A1 JP 0109496 W JP0109496 W JP 0109496W WO 0238139 A1 WO0238139 A1 WO 0238139A1
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WO
WIPO (PCT)
Prior art keywords
amino group
polymer compound
acid
drug
preparation
Prior art date
Application number
PCT/JP2001/009496
Other languages
English (en)
Japanese (ja)
Inventor
Takaaki Terahara
Kazunosuke Aida
Naruhito Higo
Shuji Sato
Original Assignee
Hisamitsu Pharmaceutical Co., Inc.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hisamitsu Pharmaceutical Co., Inc. filed Critical Hisamitsu Pharmaceutical Co., Inc.
Priority to CA002428181A priority Critical patent/CA2428181A1/fr
Priority to JP2002540725A priority patent/JP4057418B2/ja
Priority to US10/416,628 priority patent/US20040028724A1/en
Priority to EP01976871A priority patent/EP1340496A4/fr
Priority to AU2001296029A priority patent/AU2001296029A1/en
Publication of WO2002038139A1 publication Critical patent/WO2002038139A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/205—Amine addition salts of organic acids; Inner quaternary ammonium salts, e.g. betaine, carnitine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061—Polyacrylates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7076—Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising ingredients of undetermined constitution or reaction products thereof, e.g. rosin or other plant resins

Definitions

  • the present invention relates to a transdermal preparation for transdermal absorption of a drug. More specifically, the present invention relates to a patch preparation having excellent skin permeability of an active ingredient, low skin irritation, and excellent physical stability.
  • transdermal preparations are being actively developed. This transdermal absorption formulation not only compensates for these drawbacks, but is also expected to have advantages such as reduced number of administrations, improved compliance, and ease of administration and discontinuation, especially for elderly and pediatric patients. And is known to be useful. '
  • the base used in ordinary transdermal preparations has sufficient transdermal absorption of the compounded active ingredients. Is often difficult to obtain.
  • ionic drugs such as drug salts generally have extremely low permeability, and therefore, a device to enhance the percutaneous absorption of the drug through the stratum corneum of the skin. It is common to use desalted molecular form drugs for ionic drugs.
  • butterol a bronchodilator, which is used in the form of hydrochloride as an oral preparation
  • many basic drugs have poor molecular stability, and the stabilizers such as antioxidants have skin irritation.
  • attempts have been made to improve the skin permeability of the drug by forming a highly lipophilic ion pair by using a hypoallergenic organic acid for the counter ion.
  • transdermal preparation a method combining a drug with a polymer compound having an amino group has also been reported.
  • a tape preparation in which piroxicam and Eidragide E (methyl methacrylate-butyl methacrylate-dimethyl dimethylaminoethyl copolymer) are combined with a natural rubber-based adhesive Japanese Patent No. 2857082
  • a tape preparation containing acrylate, a softener, and a drug having an acidic group using Eudragit E as a preparation base Japanese Patent Application Laid-Open No.
  • the present invention has been made to solve the above-mentioned problems of the prior art, and has a base A transdermal preparation containing an acid addition salt of an amphoteric drug or an amphoteric drug, which has excellent skin permeability of medicinal ingredients, low skin irritation, and excellent physical stability
  • the purpose is to provide a prescription preparation.
  • a patch containing a basic functional group-containing drug in a salt form contains a polymer compound having a specific amount or more of an amino group. Then, it is converted into a molecular form of the drug and its permeability to the skin is improved.By adding a suitable organic acid there, ion pairs are formed efficiently and the distribution rate to the skin is increased. Therefore, it is possible to provide a patch preparation which significantly improves the skin permeability of a drug, and which is safe for the skin as an administration site, and which is excellent in content stability, physical stability of a base, and the like. Heading, the present invention has been completed.
  • the present invention relates to a polymer compound having an amino group, a drug which forms an acid addition salt, and a transdermal preparation containing a carboxylic acid and / or a salt thereof, which has an amino group.
  • the content of the polymer compound is 50% by mass or less based on the total amount of the preparation; the molar ratio of the amino group in the polymer compound is 0.5 mol or more per 1 mol of the drug;
  • the present invention relates to a transdermal preparation, characterized in that the content of the acid and / or its salt is 1 to 10 mol based on the total number of amino groups in the drug and the polymer compound.
  • the present invention provides a skin absorption comprising a drug forming an acid addition salt, comprising a polymer compound having an amino group and a carboxylic acid and / or a salt thereof.
  • the present invention relates to a method for improving skin permeability and skin irritation of a type preparation.
  • the amino group of the polymer compound having an amino group used in the present invention may be any of primary, secondary and tertiary amino groups.
  • high molecular compound having an amino group used in the present invention examples include, for example, high molecular compounds having a primary amino group such as polyaminostyrene, polyvinylamine, and chitosan, for example, dimethylamino (meth) acrylate Polymers of dialkylaminoalkyl (meth) acrylates, such as ethyl, dimethylaminoethyl (meth) acrylate, and dibutylaminoethyl (meth) acrylate, or monomers thereof.
  • high molecular compounds having a primary amino group such as polyaminostyrene, polyvinylamine, and chitosan
  • dimethylamino (meth) acrylate Polymers of dialkylaminoalkyl (meth) acrylates, such as ethyl, dimethylaminoethyl (meth) acrylate, and dibutylaminoethyl (meth) acrylate, or monomers thereof.
  • One or more of these monomers and one or more other copolymerizable monomers [eg, (meth) methyl acrylate, (meth) ethyl acrylate, (meth) acrylic acid propyl, (meth) acrylic Butyl acid, 2- (meth) acrylic acid 2-hydroxyl, (meth) acrylic acid 2-ethylhexyl, etc.) copolymer with 1 or more, polyvinyl acetate dimethylaminoacetate, polyvinyl acetate Polymer compounds having a tertiary amino group, such as polyvinylaceta-dialkylaminoacetate, polyvinyl pyridine, and the like, such as rucetylaminoacetate and polyvinyl acetate-dibutylaminoacetate. These polymers may be crosslinked using a suitable crosslinking agent. Further, it is also possible to use an acrylic adhesive used as a base of a skin absorption type preparation, in which a monomer having an amino group is
  • chitosan polyvinyl acetate methyl acetyl acetate, methyl methacrylate-butyl methacrylate-dimethylaminoethyl methacrylate copolymer (a product of Rohm Co., Ltd.).
  • Eudragit E trademark of Lahm
  • These polymer compounds having an amino group may be used alone or in combination of two or more.
  • the amount of the high molecular compound having an amino group used is 50% by mass or less based on the total amount of the preparation, and the molar ratio of the amino group in the high molecular compound is 0.5% or more with respect to 1 mol of the drug. More preferably, the amount of the polymer compound is 25% or less, the molar ratio of the amino group is 0.5 to 10 mol, and more preferably, the amount of the polymer compound is 10% or less. In addition, it is desirable that the compound is blended so that the molar ratio of amino groups is 0.5 to 5 mol. When a polymer compound having an amino group is contained in an amount of 50% or more, the physical properties of the preparation are remarkably reduced, which is not preferable for a transdermal preparation.
  • the carboxylic acids used in the present invention include, for example, acetic acid, propionic acid, isobutyric acid, hexanoic acid, octanoic acid, decanoic acid, lauric acid, myristic acid, palmitic acid, stearyl acid, isostearic acid Aliphatic monocarboxylic acids such as oxalic acid, succinic acid, glutaric acid, etc .; aliphatic aliphatic acids such as oleic acid, linoleic acid, linolenic acid, maleic acid, fumaric acid, etc.
  • Saturated carboxylic acids for example, carboxylic acids such as citric acid, lactic acid, tartaric acid, and salicylic acid; ketocarboxylic acids, such as pyruvic acid; aromatic carboxylic acids, such as phthalic acid, benzoic acid, and acetylsalicylic acid; for example, cholic acid, dexico Steroid carboxylic acids such as monolic acid and dehydrocholic acid can be mentioned.
  • salts of these carboxylic acids include alkali metal salts such as Na, K, and Li; alkaline earth metal salts such as Ca, Ba, and Mg; and ammonium salts. I can do it.
  • carboxylic acids and / or salts thereof aliphatic monocarboxylic acids and oxycarboxylic acids are more preferable, and acetic acid, propionic acid, lactic acid, and salicylic acid are particularly preferable.
  • carboxylic acids and / or their salts may be used alone or in combination of two or more.
  • the amount of these carboxylic acids and / or salts used is determined by considering the percutaneous absorption type drug, especially, the sufficient amount of permeation as a patch and the irritation to the skin. It is preferably from 0.01 to 20% by mass, more preferably from 0.1 to 15% by mass, and still more preferably from 0.1 to 10% by mass, based on the total amount of the layer. % Is desirable.
  • the compounding ratio between the drug forming the acid addition salt and the carboxylate is preferably 5: 1 to 1/10 (molar ratio).
  • the drug used in the present invention is not particularly limited as long as it is an acid addition salt-forming drug.
  • examples thereof include hypnotic sedatives (flurazepam hydrochloride, rilmazahon hydrochloride, etc.), Analgesics (butorphanol tartrate, perisoxan citrate, etc.), stimulant and stimulants (methamphetamine hydrochloride, methyl panidate hydrochloride, etc.), nerve agents (sertraline hydrochloride, fluvoxamine maleate, etc.), Local anesthetic (Lidocaine hydrochloride, Procaine hydrochloride, etc.), Urinary agents (Oxyptinin hydrochloride, etc.), Skeletal muscle relaxants (Tizanidine hydrochloride, Eperisone hydrochloride, Pridinol mesylate, etc.), Autonomic nerve agents (Carpronium chloride, Neostigmi bromide) ), Anti-parkinson agents
  • drugs may be used alone or in combination of two or more. Naturally, any form of inorganic salt or organic salt is included.
  • the amount used is 0.1 to 50% by mass with respect to the total amount of the adhesive layer, taking into account the sufficient amount of permeation as a patch preparation and irritation to the skin such as redness. %.
  • the pressure-sensitive adhesive layer of the patch preparation of the present invention contains an absorption promoter in addition to a polymer compound having an amino group, a drug forming an acid addition salt, and a carboxylic acid and / or a salt thereof.
  • absorption promoter examples include all compounds that have been conventionally recognized as having an absorption promoting effect on the skin.
  • aliphatic alcohols for example, aliphatic alcohols, fatty acid esters, fatty acid amides, aliphatic ethers, aromatic alcohols, aromatic carboxylic acid esters or ethers (the above may be either saturated or unsaturated, It may be cyclic or linearly branched.)
  • monoterpene compounds, sesquiterpene compounds for example, monoterpene compounds, sesquiterpene compounds, Azone (A zone), Azone (A zone) derivative, glycerin fatty acid esters, propylene glycol Fatty acid esters, sorbitan fatty acid esters (Span type), polysorbate type (Tween type), polyethylene glycol fatty acid esters, polyoxyethylene cured castor Oil-based (HCO-based), polyoxyethylene alkyl ethers, sucrose fatty acid esters, vegetable oils and the like.
  • lauryl alcohol myristyl alcohol, oleyl alcohol, isostearyl alcohol, cetyl alcohol, methyl laurate, hexyl laurate, diethanolamide laurate, myristyl Isopropyl acetate, myristyl myristate, octyl dodecyl myristate, cetyl palmitate, salicylic acid, methyl salicylate, ethylene glycol salicylate, methyl citrate, cresol, cetyl lactate, lauryl lactate, ethyl acetate, propyl acetate, geraniol , Thymol, eugenol, terbineol, 1-menthol, borneol, d-limonene, isoeugenol, isoborneol, nerol, d1-camphor, glycerin monocaprylate Glycerin monoplate, glycerin monolaurate,
  • Two or more of these absorption enhancers may be used as a mixture, and the amount used is determined in consideration of sufficient permeability as a patch preparation and skin irritation such as redness and edema.
  • the amount is preferably from 0.01 to 20% by mass, more preferably from 0.05 to 10% by mass, and even more preferably from 0.0 :! It is desirable to be blended in an amount of up to 5% by mass. .
  • the adhesive layer of the patch preparation of the present invention may further contain a plasticizer.
  • plasticizer examples include petroleum-based oils (eg, liquid paraffin, paraffin-based process oil, and naphthenic-based process). Oils, aromatic process oils, etc.), squalane, squalene, vegetable oils (eg olive oil, camellia oil, castor oil, Tall oil, radish oil, silicone oil, dibasic acid ester (eg, dibutyl phthalate, dioctyl phthalate, etc.), liquid rubber (eg, liquid polybutene, liquid isoprene rubber), liquid fatty acid ester (myristic acid) Isopropyl, hexyl laurate, getyl sebacate, diisopropyl sebacate), ethylene glycol, polyethylene glycol, glycol salicylate, propylene glycol, dipropylene glycol, triacetin, triethyl citrate, crotamiton, etc. Is
  • the amount of such a plasticizer should be adjusted in consideration of sufficient permeability and maintenance of sufficient cohesive strength as a patch preparation. It is desirable that the total amount be from 10 to 70% by mass, preferably from 10 to 60% by mass, and more preferably from 10 to 50% by mass, based on the total amount of the layer.
  • a rubber-based polymer As the base of the pressure-sensitive adhesive layer of the patch preparation of the present invention, a rubber-based polymer is usually used.
  • the rubber-based polymer include styrene-isoprene-styrene block copolymer (hereinafter abbreviated as SIS), isoprene rubber, polyisobutylene (hereinafter abbreviated as PIB), and styrene-butadiene.
  • SIS styrene-isoprene-styrene block copolymer
  • PIB polyisobutylene
  • SBS styrene-butadiene rubber
  • SBR styrene-butadiene rubber
  • SIS and PIB are preferable, and SIS is particularly preferable.
  • Two or more of such rubber-based polymers may be used as a mixture, and the amount of these rubber-based polymers may be adjusted in consideration of the formation of the pressure-sensitive adhesive layer and sufficient permeability. It is desirable that the amount is 5 to 60% by mass, preferably 10 to 50% by mass, more preferably 20 to 40% by mass based on the total amount of the layer. .
  • a (meth) acrylic polymer (2-ethylhexyl acrylate, methyl (meth) acrylate, butyl (meth) acrylate, or hydroxethyl is used as a base.
  • (meth) acrylate, glycidyl (meth) acrylate, or a copolymer containing at least one of (meth) acrylic acid can be used.
  • Such an acrylic polymer may be used as a mixture of two or more kinds, or may be used in combination with the rubber polymer described above.
  • the amount of these acrylic polymers is determined based on the total amount of the adhesive layer, taking into account the formation of the adhesive layer and sufficient permeability. It is desirably 2 to 88% by mass, preferably 5 to 50% by mass, and more preferably 10 to 40% by mass.
  • the pressure-sensitive adhesive layer of the adhesive preparation of the present invention may further contain a tackifying resin.
  • a tackifying resin examples include rosin derivatives (eg, rosin, glycerin ester of rosin, hydrogenated rosin, hydrogenated rosin).
  • Rosin glycerin ester, rosin pen erythritol ester, etc. alicyclic saturated hydrocarbon resin [for example, ALCON P100 (trade name of Arakawa Chemical Industry Co., Ltd.)], aliphatic hydrocarbon resin [for example, Kui Toner B170 (trade name of Zeon Corporation), terpene resin [eg, Clearon P-125 (trade name of Yashara Chemical Co., Ltd.)], maleic resin, and the like.
  • glycerin ester of hydrogenated rosin, alicyclic saturated hydrocarbon resin, aliphatic hydrocarbon resin, and terpene resin are preferable.
  • the amount of such a tackifier resin is preferably 5 to 10% by mass with respect to the total amount of the pressure-sensitive adhesive layer in consideration of sufficient adhesive strength as a patch and irritation to the skin during peeling. Preferably, it is 5 to 60% by mass, more preferably 10 to 50% by mass.
  • an antioxidant, a filler, a crosslinking agent, a preservative, an ultraviolet absorber and the like can be used.
  • Preferred antioxidants include tocoprol and their ester derivatives, ascorbic acid, ascorbic acid stearate, nordihydroguaiaretinic acid, dibutylhydroxytoluene (BHT), and butylhydroxylazole. It is listed as.
  • fillers examples include calcium carbonate, magnesium carbonate, silicates (eg, aluminum silicate, magnesium silicate, etc.), silicate, barium sulfate, calcium sulfate, calcium zincate, zinc oxide, and titanium oxide. Etc. are preferred.
  • crosslinking agent examples include thermosetting resins such as amino resin, phenol resin, epoxy resin, alkyd resin, and unsaturated polyester, isocyanate compounds, block isocyanate compounds, organic crosslinking agents, and inorganic compounds such as metals or metal compounds. Cross-linking agents are preferred.
  • ethyl ethyl paraoxybenzoate propyl paraoxybenzoate
  • Preferred are butyl paraoxybenzoate and the like.
  • Preferred examples of the ultraviolet absorber include P-aminobenzoic acid derivatives, anthranilic acid derivatives, salicylic acid derivatives, coumarin derivatives, amino acid compounds, imidazoline derivatives, pyrimidine derivatives, and dioxane derivatives.
  • Such antioxidants, fillers, cross-linking agents, preservatives, ultraviolet absorbers, etc. are preferably 10% by mass or less, more preferably 5% by mass, based on the total amount of the adhesive layer. %, More preferably 2% by mass or less.
  • the pressure-sensitive adhesive layer of the patch preparation of the present invention can be produced by any method known per se. That is, for example, a base component containing a drug may be heat-melted, coated on a release paper or a support, and then adhered to the support or release paper to obtain the present agent, or a base component containing a drug. May be dissolved in a solvent such as toluene, hexane, or ethyl acetate, spread on release paper or a support, and the solvent may be removed by drying, and then adhered to the support or release paper to obtain the present agent.
  • a solvent such as toluene, hexane, or ethyl acetate
  • the patch preparation of the present invention may have any other composition as long as the pressure-sensitive adhesive layer has the above-mentioned composition containing a polymer compound having an amino group, a carboxylic acid and / or a salt thereof, and a drug.
  • the material of each component and each component may be of any type.
  • the patch preparation of the present invention can be composed of the above-mentioned pressure-sensitive adhesive layer, a support layer for supporting the pressure-sensitive adhesive layer, and a release paper layer provided on the pressure-sensitive adhesive layer.
  • a stretchable or non-stretchable support can be used as the support layer.
  • the material is selected from cloth, nonwoven fabric, polyurethane, polyester, polyvinyl acetate, polyvinylidene chloride, polyethylene, polyethylene terephthalate, aluminum sheet, and the like, or a composite material thereof.
  • the transdermal preparation of the present invention has the above-mentioned composition containing a basic drug or amphoteric drug in the form of an acid addition salt, a polymer compound having an amino group, and a carboxylic acid and / or a salt thereof.
  • the other components and the material of each component may be of any type.
  • Acrylic polymer 2 3.0%
  • Example 5 oxyptinin hydrochloride, salicylic acid, glycerin monoforce plate and liquid paraffin were placed in a mortar, mixed well, and then mixed with the remaining components dissolved in ethyl acetate. After coating on a release paper, the solvent was removed by drying, and the resultant was bonded to a support to obtain a matrix patch preparation of the present invention.
  • oxyptinin hydrochloride, salicylic acid, glycerin monoforce plate and liquid paraffin were placed in a mortar, mixed well, and then mixed with the remaining components dissolved in ethyl acetate. After coating on a release paper, the solvent was removed by drying, and the resultant was bonded to a support to obtain a matrix patch preparation of the present invention.
  • Example 5
  • Acrylic polymer 1 1.0%
  • Example 7 Except for removing the high molecular compound having an amino group, the same components and the same preparation method as in Example 1-6 were used to prepare the corresponding matrix patch preparations, and these were used as comparative examples. 1 to 6. Comparative Example 7—1 2
  • Example 16 Except that 55% of the polymer compound having an amino group was contained in the formulation of Example 16, the same components and the same preparation method as in Examples 1-6 were applied to the corresponding matrices. Formulations were prepared and these were referred to as Comparative Examples 13 to 18 respectively. Comparative Example 1 9 1 2 2
  • Example 1 Hairless mouse skin penetration test
  • the back skin of the hairless mouse was peeled off, the dermis side was set to the receptor layer side, and the skin was attached to a flow-through cell (5 cm 2 ) in which warm water of 37 ° C. was circulated around the periphery.
  • a flow-through cell 5 cm 2
  • the preparations obtained in Example 15 and Comparative Example 15 and Comparative Example 16 Using a physiological saline solution for the receptor layer, sampling was performed every hour for up to 18 hours at a rate of 5 ml / hour (hr).
  • the receptor solution obtained every hour measures the flow rate accurately, measures the drug concentration by high performance liquid chromatography, calculates the permeation rate per hour, and calculates the unit area in the steady state.
  • the percutaneous permeation rate was determined. Table 1 shows the results.
  • the preparation obtained in each of the examples of the present invention contains the carboxylic acid and / or the salt obtained in Comparative Example 1-6 containing only the salt thereof, and amino. It can be seen that the drug skin permeation rate is significantly higher than that of the preparation obtained in Comparative Example 19-22 containing only the polymer compound having a group.
  • Test example 2 Primary irritant test on heron skin
  • Example 16 and Comparative Example 13-18 the adhesive force was measured with a probe tack tester [trade name: Probe Tack Tester 1 (Rigaku Kogyo Co., Ltd.)] and a peel measuring machine [product Name: Tensilon RTM-100 (Orientec Co., Ltd.)] and the cohesive force was measured by a cleaving machine [Product name: Tensilon RTM-100 (Orientec Co., Ltd.)]. It was measured. In addition, stringing and bleeding of the solution components were visually judged. As a result, those having no problem in the physical properties of the preparation were evaluated as “ ⁇ ”, and those having the problem were evaluated as “X”. The results are shown in Table 3. Table 3
  • the patch preparation of the present invention has a remarkably high drug skin permeation rate, the drug can be efficiently absorbed into the circulating blood via the skin. It also avoids the digestive system side effects that occur with oral administration and the central side effects that can occur with rapid increases in blood levels. Furthermore, since it has extremely low skin irritation and excellent physical stability, it is particularly effective as an external preparation for transdermal application.

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  • Health & Medical Sciences (AREA)
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  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
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  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Inorganic Chemistry (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Cette invention se rapporte à une préparation pharmaceutique adhésive du type à absorption percutanée, qui contient un sel d'addition d'acide d'un médicament basique ou amphotère, dont le principe actif possède un fort pouvoir de pénétration par perméation dans la peau et se caractérise par une réduction de son effet d'irritation sur la peau et par une excellente stabilité physique. Cette préparation comprend un polymère aminé, un médicament sous la forme d'un sel d'addition d'acide, et un acide carboxylique ou/et un sel de celui-ci, et elle se caractérise en ce que la teneur en polymère aminé est inférieure ou égale à 50 % en poids, calculé sur la base de la préparation totale, la quantité des groupes aminés contenus dans le polymère étant de 0,5 mol ou plus par mol du médicament et la quantité d'acide carboxylique ou/et de son sel étant comprise entre 1 et 10 mol par mol de la somme du médicament et des groupes aminés contenus dans le polymère.
PCT/JP2001/009496 2000-11-07 2001-10-30 Preparation pharmaceutique du type a absorption percutanee WO2002038139A1 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
CA002428181A CA2428181A1 (fr) 2000-11-07 2001-10-30 Preparation pharmaceutique du type a absorption percutanee
JP2002540725A JP4057418B2 (ja) 2000-11-07 2001-10-30 経皮吸収型製剤
US10/416,628 US20040028724A1 (en) 2000-11-07 2001-10-30 Pharmaceutical preparation of percutaneous absorption type
EP01976871A EP1340496A4 (fr) 2000-11-07 2001-10-30 Preparation pharmaceutique du type a absorption percutanee
AU2001296029A AU2001296029A1 (en) 2000-11-07 2001-10-30 Pharmaceutical preparation of percutaneous absorption type

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JP2000339524 2000-11-07
JP2000-339524 2000-11-07

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WO2002038139A1 true WO2002038139A1 (fr) 2002-05-16

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PCT/JP2001/009496 WO2002038139A1 (fr) 2000-11-07 2001-10-30 Preparation pharmaceutique du type a absorption percutanee

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US (1) US20040028724A1 (fr)
EP (1) EP1340496A4 (fr)
JP (1) JP4057418B2 (fr)
AU (1) AU2001296029A1 (fr)
CA (1) CA2428181A1 (fr)
WO (1) WO2002038139A1 (fr)

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WO2004019930A1 (fr) * 2002-08-28 2004-03-11 Hisamitsu Pharmaceutical Co., Inc. Agent de collage
WO2004019987A1 (fr) * 2002-08-28 2004-03-11 Hisamitsu Pharmaceutical Co., Inc. Timbre adhesif
WO2005041967A1 (fr) * 2003-10-31 2005-05-12 Hisamitsu Pharmaceutical Co., Inc. Preparations transdermiques et methodes d'attenuation des effets secondaires dans le cadre d'une therapie au pergolide
JP2006016382A (ja) * 2004-06-01 2006-01-19 Hisamitsu Pharmaceut Co Inc 貼付剤
WO2007129427A1 (fr) 2006-05-08 2007-11-15 Teikoku Seiyaku Co., Ltd. Préparation absorbable par voie transdermique comprenant un agent anti-démence
JPWO2005115355A1 (ja) * 2004-05-28 2008-03-27 久光製薬株式会社 貼付製剤
WO2009110351A1 (fr) * 2008-03-03 2009-09-11 久光製薬株式会社 Préparation pouvant être absorbée de façon transdermique
WO2011074636A1 (fr) 2009-12-16 2011-06-23 後藤　武 Préparation absorbée par voie transdermique d'un médicament anti-démence
WO2011074637A1 (fr) 2009-12-16 2011-06-23 後藤　武 Préparation absorbée par voie transdermique d'un médicament anti-démence
WO2011074635A1 (fr) 2009-12-16 2011-06-23 後藤　武 Préparation absorbée par voie transdermique d'un médicament anti-démence
JP2012140407A (ja) * 2010-12-13 2012-07-26 Hisamitsu Pharmaceut Co Inc 経皮吸収促進剤、ならびにそれを含有する医薬組成物および貼付剤
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US9155725B2 (en) 2008-02-27 2015-10-13 Hisamitsu Pharmaceutical Co., Inc. Adhesive skin patch and packaged product
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WO2004019987A1 (fr) * 2002-08-28 2004-03-11 Hisamitsu Pharmaceutical Co., Inc. Timbre adhesif
JP2004083519A (ja) * 2002-08-28 2004-03-18 Hisamitsu Pharmaceut Co Inc 貼付剤
KR101032282B1 (ko) * 2002-08-28 2011-05-06 히사미쓰 세이야꾸 가부시키가이샤 첩부제
WO2004019988A1 (fr) * 2002-08-28 2004-03-11 Hisamitsu Pharmaceutical Co., Inc. Patch adhesif
US8691267B2 (en) 2002-08-28 2014-04-08 Hisamitsu Pharmaceutical Co., Inc. Adhesive patch
KR100971643B1 (ko) * 2002-08-28 2010-07-22 히사미쓰 세이야꾸 가부시키가이샤 첩부제
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WO2005041967A1 (fr) * 2003-10-31 2005-05-12 Hisamitsu Pharmaceutical Co., Inc. Preparations transdermiques et methodes d'attenuation des effets secondaires dans le cadre d'une therapie au pergolide
JPWO2005115355A1 (ja) * 2004-05-28 2008-03-27 久光製薬株式会社 貼付製剤
JP2006016382A (ja) * 2004-06-01 2006-01-19 Hisamitsu Pharmaceut Co Inc 貼付剤
WO2007129427A1 (fr) 2006-05-08 2007-11-15 Teikoku Seiyaku Co., Ltd. Préparation absorbable par voie transdermique comprenant un agent anti-démence
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JP5122445B2 (ja) * 2006-05-08 2013-01-16 帝國製薬株式会社 抗認知症薬物の経皮吸収製剤
JP6054013B2 (ja) * 2008-02-27 2016-12-27 久光製薬株式会社 貼付製剤
US9155725B2 (en) 2008-02-27 2015-10-13 Hisamitsu Pharmaceutical Co., Inc. Adhesive skin patch and packaged product
US8871249B2 (en) 2008-02-27 2014-10-28 Hisamitso Pharmaceutical Co., Inc. Medicated patch
WO2009110351A1 (fr) * 2008-03-03 2009-09-11 久光製薬株式会社 Préparation pouvant être absorbée de façon transdermique
JP5618822B2 (ja) * 2008-03-03 2014-11-05 久光製薬株式会社 経皮吸収製剤
WO2011074635A1 (fr) 2009-12-16 2011-06-23 後藤　武 Préparation absorbée par voie transdermique d'un médicament anti-démence
JPWO2011074635A1 (ja) * 2009-12-16 2013-04-25 後藤　武 抗認知症薬物の経皮吸収製剤
WO2011074637A1 (fr) 2009-12-16 2011-06-23 後藤　武 Préparation absorbée par voie transdermique d'un médicament anti-démence
JP5800715B2 (ja) * 2009-12-16 2015-10-28 帝國製薬株式会社 抗認知症薬物の経皮吸収製剤
WO2011074636A1 (fr) 2009-12-16 2011-06-23 後藤　武 Préparation absorbée par voie transdermique d'un médicament anti-démence
JP2012140407A (ja) * 2010-12-13 2012-07-26 Hisamitsu Pharmaceut Co Inc 経皮吸収促進剤、ならびにそれを含有する医薬組成物および貼付剤
US9980920B2 (en) 2013-09-11 2018-05-29 Medrx Co., Ltd. Base composition for tape agent
WO2017094337A1 (fr) * 2015-12-04 2017-06-08 ニチバン株式会社 Timbre transdermique

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EP1340496A1 (fr) 2003-09-03
AU2001296029A1 (en) 2002-05-21
JPWO2002038139A1 (ja) 2004-03-11
US20040028724A1 (en) 2004-02-12
CA2428181A1 (fr) 2002-05-16
JP4057418B2 (ja) 2008-03-05
EP1340496A4 (fr) 2004-04-14

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